SYNTHESIS AND PROTEIN-KINASE-C INHIBITORY ACTIVITIES OF BALANOL ANALOGS WITH REPLACEMENT OF THE PERHYDROAZEPINE MOIETY

Balanol is a potent protein kinase C (PKC) inhibitor that is structura lly composed of a benzophenone diacid, a 4-hydroxybenzamide, and a per hydroazepine ring. A number of balanol analogs in which the perhydroaz epine moiety is replaced have been synthesized and their biological ac tivities evaluated against both PKC and cAMP-dependent kinase (PKA). T he results suggested that the activity and the isozyme/kinase selectiv ity of these compounds are largely related to the conformation about t his nonaromatic structural element of the molecules.